MalariaPhase 1NCT00740090
Malaria Vaccine for Children in Mali
A Phase 1 study testing AMA1-C1/Alhydrogel plus CPG 7909 in people with Malaria and Malaria Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Mali.
Trial summary
This study will evaluate the safety and immune response of children to an experimental malaria vaccine called AMA1-C1/Alhydrogel® (Registered Trademark) + CPG 7909. Malaria is an infection of red blood cells caused by a parasite, Plasmodium falciparum, that is spread by certain kinds of mosquitoes. Read more about this study
- Who is it for?
- Ages 1 year to 3 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria, Malaria Infection
- What is being tested?
- AMA1-C1/Alhydrogel plus CPG 7909
- How many people
- 200 participants
- Where
- 1 siteMali
- Study dates
- 11 Aug 2008to 9 Jun 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 3 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Males or females aged greater than or equal to 1 to less than 4 years
- Known residents of the village of Bancoumana, Mali or its surrounding area
- Good general health as determined by means of the screening procedure
- Available for the duration of the trial (24 months from enrollment)
- Willingness to have child participate in the study as evidenced by parents/legal guardians signing or fingerprinting the informed consent document
Who cannot join
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, chronic infectious or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
- Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the volunteer or the parent/legal guardian to understand and cooperate with the study protocol.
- Pre-existing known autoimmune diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, or autoimmune thrombocytopenia.
- Laboratory evidence of possible autoimmune disease determined by anti-dsDNA titer that equals or exceeds 25 IU.
- Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than the upper limit of normal of the testing laboratory).
- Laboratory evidence of renal disease (serum creatinine greater than the upper limit of normal of the testing laboratory, or more than trace protein or blood on urine dipstick testing confirmed by repeat testing).
Show all 25Show fewer
- Laboratory evidence of hematologic disease (absolute leukocyte count less than 3000/mm(3) or greater than 14,500/mm(3), absolute lymphocyte count less than 1000/mm(3), platelet count less than 120,000/mm(3), or hemoglobin less than 8.5 g/dL).
- Other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol.
- Participation in another investigational vaccine or drug trial within 30 days of starting this study, or while this study is ongoing.
- History of a severe allergic reaction or anaphylaxis.
- History of allergy to nickel.
- Severe asthma. This will be defined as:
- Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past two years or that requires the use of oral or parenteral corticosteroids.
- Clinically significant reactive airway disease that does not respond to bronchodilators.
- Positive screening test for anti-Hepatitis C virus (anti-HCV).
- Positive screening test for Hepatitis B surface antigen (HBsAg).
- Known immunodeficiency syndrome.
- Use of systemic corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study.
- History of a surgical splenectomy.
- Receipt of blood products within the past 6 months.
- Previous receipt of an investigational malaria vaccine or of rabies vaccine.
- History of use of chloroquine or related compounds (amodiaquine or primaquine) within 8 weeks of study entry. Chloroquine and related compounds have the potential to interfere with CPG-induced activation of B cells and plasma dendritic cells.
- Previous administration of Verorab Trademark vaccine.
- Known thrombocytopenia or bleeding disorders.
- Known allergy to neomycin (a component of Verorab Trademark).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1, Randomized, Double-Blind, Dose-Escalating Study of the Safety, Reactogenicity, and Immunogenicity of the AMA1-C1/Alhydrogel+CPG 7909 Vaccine for Plasmodium Falciparum Malaria in Children in Mali
This study will evaluate the safety and immune response of children to an experimental malaria vaccine called AMA1-C1/Alhydrogel® (Registered Trademark) + CPG 7909. Malaria is an infection of red blood cells caused by a parasite, Plasmodium falciparum, that is spread by certain kinds of mosquitoes. It affects at least 300 million people worldwide each year, with more than 1 million deaths, mostly among children less than 5 years of age in sub-Saharan Africa. Malaria is the leading cause of death and illness among the general population of Mali in West Africa. Increasing drug resistance to P. falciparum and widespread resistance of mosquitoes to pesticides are reducing the ability to control the disease through these strategies. AMA1 C1 is made from a synthetic protein similar to a P. falciparum protein. It is combined with Alhydrogel and CPG 7909, substances added to vaccines to make them work better.
Children between 1 and 4 years of age who live in Bancoumana, Mali, and are in general good health may be eligible for this study. Candidates are screened with a medical history, physical examination, and blood and urine tests.
Read more
Participants are randomly assigned to receive three injections (shots) of either AMA1-C1 or a control rabies inactivated vaccine called Imovax® (Registered Trademark). The shots are given in the thigh muscle on study days 0, 56 and 180. After each shot, participants are observed in the clinic for 30 minutes. They return to the clinic for a physical examination six or seven times between each shot and then four more times over a 9-month period after the last shot. Blood samples are drawn at several of these visits to check for side effects of the vaccine and to measure the response to it. The total duration of the study is 21 months.
...
Read the detailed description
Globally, the Plasmodium falciparum parasite is responsible for at least 300 million acute cases of malaria each year, with more than 1 million deaths. Approximately 90 percent of these deaths, the majority in children under 5 years of age, occur in Africa due to infection with Plasmodium falciparum. Morbidity and mortality caused by malaria also has significant direct and indirect costs on the economic development of the endemic countries. It is estimated that malaria accounts for 40 percent of public health expenditures, more than 30 percent of inpatient admissions, and approximately 50 percent of outpatient visits in some African countries. These factors, as well as growing drug resistance of the parasite, widespread resistance of mosquitoes to insecticide, and increased human travel necessitate the need for new approaches to malaria control and eradication. A vaccine that could reduce both mortality and morbidity secondary to Plasmodium falciparum infection would be a valuable resource in the fight against this disease.
Over time, people living in endemic areas develop natural immunity to Plasmodium falciparum as a result of repeated infection. Consequently, children who survive to 7 to 10 years of age rarely succumb to life-threatening disease despite frequent infection. This acquired immunity is mediated in part by blood-stage parasite-specific antibodies. Thus, parasite proteins expressed during the blood-stage have been proposed to be good candidates for inclusion in a vaccine. The purpose of a blood-stage vaccine is to elicit immune responses that either destroy the parasite in the blood stream or inhibit the parasite from infecting red blood cells, thus reducing or preventing complications of the disease.
A number of Plasmodium falciparum merozoite antigens have been identified as promising blood-stage vaccine candidates, including Apical Membrane Antigen 1 (AMA1). The precise role of AMA1 in the parasite is unknown; however, it is critical in the erythrocyte invasion process across divergent Plasmodium species and for blood-stage multiplication of the parasite. Recent analysis of the Plasmodium falciparum proteome detected expression of AMA1 in the sporozoite stage and suggests an additional role for AMA1 during the liver-stage invasion. Therefore, an immune response against AMA1 may have an effect on liver-stage parasites as well as having an impact on blood-stage parasites, thus protecting the host by multiple immune mechanisms. Human and animal anti-AMA1 antibodies inhibit merozoite invasion in vitro and correlate with protection against parasite challenge in animal models. T-cells specific for Plasmodium falciparum AMA1 have also been demonstrated in individuals living in endemic areas.
At least 68 known amino acid polymorphisms of AMA1 have been demonstrated, and animal studies have shown that the polymorphisms in AMA1 are not immunologically silent. The combination of two or more divergent AMA1 sequences within a single vaccine formulation may reduce evasion of the host immune response by some Plasmodium falciparum field isolates.
- Conditions
- Malaria, Malaria Infection
- Being tested
- AMA1-C1/Alhydrogel plus CPG 7909
- Keywords
- Malaria, Reactogenicity, Safety, Immunogenicity, Maleria Endemic, Plasmodium Falciparum, Dose Escalating
- Medical subject headings
- Malaria, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMA1-C1/Alhydrogel plus CPG 7909Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence and severity of systemic and local adverse events.
Secondary outcomes (1)
Antibody response determined by ELISA, to the AMA1-FVO and AMA1-3D7 proteins at selected time points. Inhibition of P. falciparum FVO and 3D7 parasite growth in vitro determined at selected time points.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2008 (estimated)
- Study start11 Aug 2008
- Primary completion9 Jun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 200 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00740090
- Sponsor's protocol ID
- 999908194
- Other IDs
- 08-I-N194
- Status last verified
- 9 Jun 2009
- First submitted
- 21 Aug 2008
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Sachs J, Malaney P. The economic and social burden of malaria. Nature. 2002 Feb 7;415(6872):680-5. doi: 10.1038/415680a.
PubMed 11832956Richie TL, Saul A. Progress and challenges for malaria vaccines. Nature. 2002 Feb 7;415(6872):694-701. doi: 10.1038/415694a.
PubMed 11832958Triglia T, Healer J, Caruana SR, Hodder AN, Anders RF, Crabb BS, Cowman AF. Apical membrane antigen 1 plays a central role in erythrocyte invasion by Plasmodium species. Mol Microbiol. 2000 Nov;38(4):706-18. doi: 10.1046/j.1365-2958.2000.02175.x.
PubMed 11115107
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Randomized, Double-Blind, Dose-Escalating Study of the Safety, Reactogenicity, and Immunogenicity of the AMA1-C1/Alhydrogel+CPG 7909 Vaccine for Plasmodium Falciparum Malaria in Children in Mali
- ClinicalTrials.gov ID
- NCT00740090
- Acronym / sponsor ID
- 999908194
- Conditions
- Malaria, Malaria Infection
- Keywords
- Malaria, Reactogenicity, Safety, Immunogenicity, Maleria Endemic, Plasmodium Falciparum, Dose Escalating
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 11 Aug 2008
- Primary completion
- 9 Jun 2009 (actual)
- First posted
- 22 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety and immune response of children to an experimental malaria vaccine called AMA1-C1/Alhydrogel® (Registered Trademark) + CPG 7909. Malaria is an infection of red blood cells caused by a parasite, Plasmodium falciparum, that is spread by certain kinds of mosquitoes. It affects at least 300 million people worldwide each year, with more than 1 million deaths, mostly among children less than 5 years of age in sub-Saharan Africa. Malaria is the leading cause of death and illness among the general population of Mali in West Africa. Increasing drug resistance to P. falciparum and widespread resistance of mosquitoes to pesticides are reducing the ability to control the disease through these strategies. AMA1 C1 is made from a synthetic protein similar to a P. falciparum protein. It is combined with Alhydrogel and CPG 7909, substances added to vaccines to make them work better.
Children between 1 and 4 years of age who live in Bancoumana, Mali, and are in general good health may be eligible for this study. Candidates are screened with a medical history, physical examination, and blood and urine tests.
Participants are randomly assigned to receive three injections (shots) of either AMA1-C1 or a control rabies inactivated vaccine called Imovax® (Registered Trademark). The shots are given in the thigh muscle on study days 0, 56 and 180. After each shot, participants are observed in the clinic for 30 minutes. They return to the clinic for a physical examination six or seven times between each shot and then four more times over a 9-month period after the last shot. Blood samples are drawn at several of these visits to check for side effects of the vaccine and to measure the response to it. The total duration of the study is 21 months.
...
Detailed description
Globally, the Plasmodium falciparum parasite is responsible for at least 300 million acute cases of malaria each year, with more than 1 million deaths. Approximately 90 percent of these deaths, the majority in children under 5 years of age, occur in Africa due to infection with Plasmodium falciparum. Morbidity and mortality caused by malaria also has significant direct and indirect costs on the economic development of the endemic countries. It is estimated that malaria accounts for 40 percent of public health expenditures, more than 30 percent of inpatient admissions, and approximately 50 percent of outpatient visits in some African countries. These factors, as well as growing drug resistance of the parasite, widespread resistance of mosquitoes to insecticide, and increased human travel necessitate the need for new approaches to malaria control and eradication. A vaccine that could reduce both mortality and morbidity secondary to Plasmodium falciparum infection would be a valuable resource in the fight against this disease.
Over time, people living in endemic areas develop natural immunity to Plasmodium falciparum as a result of repeated infection. Consequently, children who survive to 7 to 10 years of age rarely succumb to life-threatening disease despite frequent infection. This acquired immunity is mediated in part by blood-stage parasite-specific antibodies. Thus, parasite proteins expressed during the blood-stage have been proposed to be good candidates for inclusion in a vaccine. The purpose of a blood-stage vaccine is to elicit immune responses that either destroy the parasite in the blood stream or inhibit the parasite from infecting red blood cells, thus reducing or preventing complications of the disease.
A number of Plasmodium falciparum merozoite antigens have been identified as promising blood-stage vaccine candidates, including Apical Membrane Antigen 1 (AMA1). The precise role of AMA1 in the parasite is unknown; however, it is critical in the erythrocyte invasion process across divergent Plasmodium species and for blood-stage multiplication of the parasite. Recent analysis of the Plasmodium falciparum proteome detected expression of AMA1 in the sporozoite stage and suggests an additional role for AMA1 during the liver-stage invasion. Therefore, an immune response against AMA1 may have an effect on liver-stage parasites as well as having an impact on blood-stage parasites, thus protecting the host by multiple immune mechanisms. Human and animal anti-AMA1 antibodies inhibit merozoite invasion in vitro and correlate with protection against parasite challenge in animal models. T-cells specific for Plasmodium falciparum AMA1 have also been demonstrated in individuals living in endemic areas.
At least 68 known amino acid polymorphisms of AMA1 have been demonstrated, and animal studies have shown that the polymorphisms in AMA1 are not immunologically silent. The combination of two or more divergent AMA1 sequences within a single vaccine formulation may reduce evasion of the host immune response by some Plasmodium falciparum field isolates.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 1 year to 3 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Males or females aged greater than or equal to 1 to less than 4 years
- Known residents of the village of Bancoumana, Mali or its surrounding area
- Good general health as determined by means of the screening procedure
- Available for the duration of the trial (24 months from enrollment)
- Willingness to have child participate in the study as evidenced by parents/legal guardians signing or fingerprinting the informed consent document
Key exclusion criteria (25 listed)
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, chronic infectious or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
- Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the volunteer or the parent/legal guardian to understand and cooperate with the study protocol.
- Pre-existing known autoimmune diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, or autoimmune thrombocytopenia.
- Laboratory evidence of possible autoimmune disease determined by anti-dsDNA titer that equals or exceeds 25 IU.
- Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than the upper limit of normal of the testing laboratory).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMA1-C1/Alhydrogel plus CPG 7909 | Drug | – |
Primary outcome
The incidence and severity of systemic and local adverse events.
1 secondary outcome
Antibody response determined by ELISA, to the AMA1-FVO and AMA1-3D7 proteins at selected time points. Inhibition of P. falciparum FVO and 3D7 parasite growth in vitro determined at selected time points.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 11832956Sachs J, Malaney P. The economic and social burden of malaria. Nature. 2002 Feb 7;415(6872):680-5. doi: 10.1038/415680a.
- Background: PubMed 11832958Richie TL, Saul A. Progress and challenges for malaria vaccines. Nature. 2002 Feb 7;415(6872):694-701. doi: 10.1038/415694a.
- Background: PubMed 11115107Triglia T, Healer J, Caruana SR, Hodder AN, Anders RF, Crabb BS, Cowman AF. Apical membrane antigen 1 plays a central role in erythrocyte invasion by Plasmodium species. Mol Microbiol. 2000 Nov;38(4):706-18. doi: 10.1046/j.1365-2958.2000.02175.x.
Related trials for Malaria
Active, not recruitingObservational study
Trajectories and Mechanisms of Recovery From Malaria: An Observational Study
Malaria
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Recruiting
The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
Iron Deficiencies
RecruitingObservational study
Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali
Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMA1-C1/Alhydrogel plus CPG 7909 in people with Malaria and Malaria Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Mali.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mali. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The incidence and severity of systemic and local adverse events.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00740090, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.